Prolonged remissions of childhood acute lymphocytic leukemia are often terminated by central nervous system relapse of the disease. The use of 2400 rads of cobalt-60 craniospinal or cranial irradiation plus intrathecal methotrexate shortly after the initial hematological remission was found to decrease considerably the incidence of central nervous system complication. Because children with leukemia now survive for many years and because the long-term effects of such intensive radiotherapy are unknown, a long-term study was planned by us to determine the neuropsychological effects of such therapy on relatively normal central nervous systems of children with leukemia. Serial neurological and psychological examinations were started in 2 groups of such children. In a retrospective study, 11 children with acute lymphocytic leukemia who received 2400 rads of prophylactic craniospinal irradiation were compared with 12 children with the same illness who did not receive irradiation during initial treatment. In a prospective study, 34 acute lymphocytic leukemia patients receiving craniospinal irradiation or cranial irradiation plus intrathecal methotrexate were compared with a group of 27 children with solid tumors who received irradiation to parts of the body other than the cranium. The objective of the repeated neurological and psychological examinations before irradiation and at intervals for several years after irradiation is to determine possible changes in intelligence, scholastic achievement, perceptual motor functioning and emotional adjustment.